caa a22 4500 445334339 CHVBK 20180317142748.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1245/s10434-011-1569-7 doi (NATIONALLICENCE)springer-10.1245/s10434-011-1569-7 Importin-α1 as a Novel Prognostic Target for Hepatocellular Carcinoma [Elektronische Daten] [Kenichiro Yoshitake, Shinji Tanaka, Kaoru Mogushi, Arihiro Aihara, Ayano Murakata, Satoshi Matsumura, Yusuke Mitsunori, Mahmut Yasen, Daisuke Ban, Norio Noguchi, Takumi Irie, Atsushi Kudo, Noriaki Nakamura, Hiroshi Tanaka, Shigeki Arii] Background: Perturbations in the nuclear microenvironment, including transport systems, play a critical role in malignant progression, but the nuclear import abnormalities remain unclear in hepatocarcinogenesis. We analyzed the role of importin in hepatocellular carcinoma (HCC). Methods: Gene expression profiling of the importin family was performed in HCC tissues. The significance of importin protein expression was analyzed in vitro as well as clinicopathologically. Results: According to the microarray profiles, the importin-α1 was dominantly overexpressed in HCC tissues as compared to the adjacent noncancerous tissues. By means of human HCC cell lines, a knockdown of importin-α1 by its siRNA greatly reduced cellular proliferation by 15.2-26.6% (P<0.005). Immunohistochemical analysis on tissue samples demonstrated cancer-specific overexpression in 36.3% of HCCs. The overexpression of importin-α1 was correlated statistically with high levels of alfa-fetoprotein (P=0.0017), the tumor number (P=0.0116), histological dedifferentiation (P=0.0054), tumor morphology (P=0.0433), portal vein invasion (P=0.0007), hepatic vein invasion (P=0.0081), Fc (P=0.0367), Fc-inf (P=0.0122), and the tumor, node, metastasis stage (P=0.0026); this resulted in a significantly poorer prognosis in both overall survival (P=0.0164) and recurrence-free survival (P=0.0101). Multivariate analysis of recurrence-free survival revealed importin-α1 expression to be a statistically significant factor (P=0.0361). In addition, early recurrence after curative resection was observed more frequently in the importin-α1-positive group as compared to the negative group (P=0.0023). The multivariate analysis identified importin-α1 as the only independent predictor of early recurrence after HCC resection (odds ratio=5.291, P=0.0191). Conclusions: Because importin-α1 might be closely associated with HCC progression, further analysis should be pursued to evaluate it as a novel prognostic target. Society of Surgical Oncology, 2011 Yoshitake Kenichiro Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut Tanaka Shinji Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut Mogushi Kaoru Information Center for Medical Sciences, Tokyo Medical and Dental University, Tokyo, Japan aut Aihara Arihiro Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut Murakata Ayano Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut Matsumura Satoshi Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut Mitsunori Yusuke Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut Yasen Mahmut Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut Ban Daisuke Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut Noguchi Norio Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut Irie Takumi Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut Kudo Atsushi Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut Nakamura Noriaki Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut Tanaka Hiroshi Information Center for Medical Sciences, Tokyo Medical and Dental University, Tokyo, Japan aut Arii Shigeki Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut Annals of Surgical Oncology Springer-Verlag 18/7(2011-07-01), 2093-2103 1068-9265 18:7<2093 2011 18 10434 https://doi.org/10.1245/s10434-011-1569-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1245/s10434-011-1569-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yoshitake Kenichiro Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Tanaka Shinji Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Mogushi Kaoru Information Center for Medical Sciences, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Aihara Arihiro Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Murakata Ayano Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Matsumura Satoshi Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Mitsunori Yusuke Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Yasen Mahmut Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Ban Daisuke Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Noguchi Norio Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Irie Takumi Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Kudo Atsushi Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Nakamura Noriaki Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Tanaka Hiroshi Information Center for Medical Sciences, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Arii Shigeki Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 773 0- Annals of Surgical Oncology Springer-Verlag 18/7(2011-07-01), 2093-2103 1068-9265 18:7<2093 2011 18 10434 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer